This invention relates to a method of reducing residual monomers, polymerization solvents and other impurities particularly from certain coarse or oversized fat imbibing, fat retaining polymer beads. It is more particularly directed to a method whereby these impurities can be reduced by bringing the polymer beads into contact with a gas in the supercritical state.
Certain fat imbibing, fat retaining polymers are known from U.S. Pat. No. 4,432,968 to have especially desirable utility in controlling the body weight of animals, including mammals such as human beings. These polymers are described as pharmacologically-acceptable, solid, particulate, crosslinked, indigestible, fat imbibing, fat retaining, polymers characterized in that they swell in liquid lard, contain less than 100 ppm of residual monomers for small and intermediate size particles but less than 500 ppm for oversized particles and have a volume average particle diameter of from about 0.05 to about 2000 microns.
The polymers are required to be essentially chemically inert in the gastrointestinal tract for pharmacological acceptability and, therefore, should be essentially free of not only unreacted monomers, but also of unreacted initiators, inhibitors, crosslinking agents or the like which are either biologically active or toxic, or chemically reactive with the ingesta. They must be void of any amount of residual solvent, catalysts, etc., that could cause detrimental side effects or vitiate the fat imbibition and weight control.
Previously, the polymers, whether prepared by emulsion or suspension polymerization, were recovered and worked up by conventional techniques such as filtration or screening to remove any coagulum or large-particle waste, dialysis, lyophilization, or particularly, with particle sizes on the order of 0.15 microns and larger, by filtration to separate the reaction medium, alcohol precipitation, washing with lower alkanols, steam distillation or other known techniques.
The preferred technique for making larger particles, e.g. from about 0.3 to 0.5 microns and larger consisted of suspension polymerization and the previous known purification technique for such particles called for passing the suspension through a screen to remove any large coagulum waste, then mixing with 10 parts by volume isopropanol. The particles were allowed to settle, and supernatant liquid removed by decantation. Washing with isopropanol was repeated, if desired. The washed polymer particles were separated by decantation, centrifugation, evaporation, or filtration and used directly or suspended in an aqueous carrier.
In all instances, preferably, purification was achieved by isolating the material as a filter cake and then sequentially washing the intact filter cake with deionized water and then an alcohol such as, for example, 190 proof ethanol or isopropanol, under pressure.
In the past, the size of the polymer bead was inversely related to their effectiveness in absorbing dietary fat. For a given amount of polymer administered, the contact with dietary fat and rate of fat absorption is enhanced as the ratio of surface area to weight of the polymer increases. Thus, smaller particles or so-called fine beads, such as from 100-500 Angstrom units to 5 microns, generally imbibes fat more rapidly and were generally believed more effective on a weight basis than intermediate size beads from 5 to about 80 microns in diameter, which were, in turn, believed more effective than particles in about the 80 to 380 micron range.
However, more recent studies indicate that the acidic gastric juices and more particularly the aqueous surfactant environment of the intestinal lumen substantially reduces the effectiveness of fine and intermediate size polymer beads by hydolytically attacking the imbibed triglycerides or fat. Although a number of means for reinforcing the surface resistance of the small and intermediate size beads have been employed, the most effective insurance against hydrolytic attack has proven to be increasing the diameter of the beads. Accordingly, coarse or oversize beads of about 80 to about 2000 microns have become more important and effective in weight control administration.
Unfortunately, alcohol extraction of coarse or oversize beads has proven to be ineffective. The removal of residual monomers and solvents occurs at a very slow rate of diffusion and the amount of extraction is much lower than that of the fine or intermediate size beads.
The need, therefore, exists for a simple inexpensive method for reducing the esidual monomers, solvents and other impurities from oversize or coarse antiobesity (fat imbibing and fat retaining) polymer beads.